crossing96/oncoscreening huggingface dataset:
Novel glycoprotein SBSPON suppressed bladder cancer through the AKT signal pathway by inhibiting HSPA5 membrane translocation.	Bladder cancer poses severe threats to human health due to its aggressive nature and resistance to drug treatment; however, the underlying mechanisms have not been fully investigated. In the present study, we identify SBSPON (Somatomedin B and Thrombospondin Type 1 Domain Containing) as a novel tumor suppressor. The expression of SBSPON was downregulated in bladder cancer and correlated with poor overall survival. SBSPON suppressed the proliferation and migration ability of bladder cancer cells in vitro, and inhibited tumor growth of bladder cancer cells in vivo. Genetic ablation of Sbspon in mice significantly accelerated the progression of N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) induced bladder cancer. Mechanistically, SBSPON is a novel HSPA5 binding glycoprotein. SBSPON functioned through binding to HSPA5 and inhibiting its membrane translocation, resulting in an inactivated AKT signaling pathway. More importantly, SBSPON inhibited the cisplatin resistance of bladder cancer cells by reducing the inhibitory effect of HSPA5 on apoptosis. In summary, the novel glycoprotein SBSPON functions as a tumor suppressor and inhibits resistance to cisplatin in bladder cancer. This may provide novel therapeutic strategies for bladder cancer treatment.	bladder
Artificial intelligence in muscle-invasive bladder cancer: opportunities, challenges, and clinical impact.	PURPOSE OF REVIEW: Muscle-invasive bladder cancer (MIBC) represents an aggressive malignancy with significant morbidity and mortality. Recent advances in artificial intelligence (AI) offer promising opportunities to enhance patient care across the entire MIBC management spectrum. This comprehensive review examines the current state and future potential of AI applications in MIBC, from diagnosis through treatment to response assessment. RECENT FINDINGS: In the diagnostic domain, AI systems demonstrate superior accuracy in cystoscopic cancer detection and staging, with deep learning models achieving high performance in differentiating muscle-invasive from noninvasive disease. For treatment planning, AI facilitates precise tumor delineation for radiotherapy, automates adaptive planning, and supports surgical decision-making through predictive lymph node involvement models. In treatment response evaluation, machine learning algorithms show encouraging results in predicting neoadjuvant chemotherapy outcomes, while radiomics and quantitative imaging biomarkers enable early response assessment. Despite these advances, significant challenges persist, including methodological limitations, dataset heterogeneity, workflow integration barriers, and regulatory uncertainties. Future directions should prioritize prospective clinical validation, federated learning approaches to address data scarcity, development of interpretable AI models, and interdisciplinary collaboration. SUMMARY: The integration of AI in MIBC management represents a paradigm shift toward personalized medicine, with the potential to improve diagnostic accuracy, optimize treatment selection, and enhance response prediction.	bladder
Neoadjuvant Pembrolizumab and Accelerated Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Nonurothelial Histologic Subtypes of Muscle-invasive Bladder Cancer: A Phase 2 Trial.	Muscle-invasive bladder cancer (MIBC) with histologic subtypes represents a clinical challenge because of poor responses to conventional therapies and under-representation in clinical trials. This single-center phase 2 trial evaluated the combination of neoadjuvant pembrolizumab and accelerated methotrexate, vinblastine, doxorubicin, and cisplatin (aMVAC) chemotherapy in patients with pure or predominant nonurothelial histologies. Seventeen patients were enrolled, with squamous differentiation being the most common variant. The primary endpoint, a pathologic complete response (pCR), was achieved in nine of 17 patients (53%), with an additional patient achieving ypTisN0 (downstaging rate 59%) and another achieving a clinical complete response. Grade ≥3 toxicities were observed in 47% of patients, primarily attributable to aMVAC. At median follow-up of 35 mo (range 11-48) the estimated 2-yr event-free survival (EFS) and overall survival rates were 64% (95% confidence interval 32-84%) and 79% (95% confidence interval 47-93%), respectively. Preliminary biomarker analysis did not reveal significant correlations between immune-cell subsets at baseline and pCR or EFS. These findings suggest that chemoimmunotherapy is a very promising approach for MIBC with histology subtypes. Larger studies are warranted to further refine therapeutic strategies.	bladder
NR4A3 regulates anoikis resistance and metastasis of bladder cancer through EWSR1.	Bladder cancer (BLCA) is a common urinary malignancy with high metastatic potential. However, the mechanisms underlying its progression remain unclear. This study aimed to investigate the role and regulatory mechanisms of NR4A3, a nuclear receptor involved in apoptosis and tumor suppression, in BLCA progression, particularly its impact on anoikis resistance and metastasis. NR4A3 expression levels were analyzed using the GEPIA database. Functional studies were conducted by overexpressing NR4A3 in adherent and suspension-cultured BLCA cells. Apoptosis, invasion, migration, and ER stress marker (Bip and CHOP) expression were evaluated. Subcutaneous and lung metastasis models in BALB/c nude mice were used for in vivo validation. GEPIA analysis showed that NR4A3 is significantly downregulated in BLCA. NR4A3 overexpression increased apoptosis, reduced invasion and migration, and upregulated Bip and CHOP expression. In vivo, NR4A3 overexpression significantly reduced lung metastasis in BALB/c nude mice (n = 8 per group, p < .001). Mechanistically, NR4A3 promoted ER stress by regulating the EWSR1/Ezrin pathway, thereby suppressing anoikis resistance. NR4A3 functions as a tumor suppressor in BLCA by enhancing endoplasmic reticulum stress and inhibiting anoikis resistance through the EWSR1/Ezrin pathway. It may serve as a promising therapeutic target for metastatic BLCA.	bladder
Invasive urothelial carcinoma with chordoid and myxoid features shows increased RAS/RAF pathway alterations.	Invasive urothelial carcinoma (UCa) with chordoid and myxoid features is an uncommon but previously described subtype of UCa composed of distinctive elongated nests and cords of tumor cells floating within a prominent myxoid stroma. The molecular features of chordoid and myxoid UCa are not known. We identified 9 cases of UCa with chordoid and myxoid features and performed a comprehensive next generation sequencing assay, targeting the chordoid and myxoid component. The cases included 7 TURBT and 2 nephroureterectomies in which the chordoid/myxoid component ranged from 10 to 80 % (mean 47 %). Available immunohistochemistry in the chordoid and myxoid component showed p63+ (9/9) and GATA3+ (8/9), supporting UCa. All cases were largely negative for SOX10 and CDX2 (one case showed weak CDX2 staining). On molecular analysis, chordoid and myxoid UCa showed a molecular profile typical of conventional UCa, with recurrent alterations in TERTp (7/9), chromatin remodeling genes (8/9) and cell cycle pathway genes (8/9). A high rate of DNA damage repair gene alterations was also seen (6/9). Interestingly, 5/9 cases demonstrated recurring alterations in RAS/RAF pathway genes, a finding typically more frequently seen in primary adenocarcinomas of the urinary bladder and less common in conventional UCa, and also suggesting possible alternative therapies for these patients. In conclusion, chordoid and myxoid UCa shows a genomic profile with both urothelial and adenocarcinoma features. Furthermore, the molecular profile reveals potentially actionable therapeutic targets in the RAS/RAF and DNA damage repair pathways and high tumor mutational burden.	bladder
Novel UF-5000-based Detection, Integrating Inflammatory Parameters, for Urothelial Carcinoma of the Urinary Bladder.	"BACKGROUND/AIM: Urothelial carcinoma (UC) is the most common epithelial bladder malignancy. Although urine cytology is widely used for screening, its sensitivity in detecting low-grade UC is limited. This study evaluated the diagnostic accuracy of the research-use parameter ""Atyp.C"" from the fully automated urine particle analyzer UF-5000, in combination with the neutrophil-to-lymphocyte ratio (NLR), for UC detection. PATIENTS AND METHODS: Urine samples from 57 noninvasive UC, 41 invasive UC, and 61 non-UC cases (n=159) were examined at Kurume University Hospital between 2020 and 2023. Specimens with atypical cells were excluded from the study. Receiver operating characteristic curve analysis was conducted using Atyp.C data from the UF-5000 to determine the optimal cutoff value. An UC detection algorithm incorporating the NLR was examined using the AI platform DataRobot, and its diagnostic accuracy was assessed. RESULTS: The diagnostic accuracy for invasive UC was assessed using an Atyp.C cut-off of 0.1/μl, yielding an area under the curve (AUC) of 0.824, sensitivity 70.7%, and specificity 90.3%. Noninvasive UC showed lower accuracy (AUC=0.565; sensitivity, 22.8%; specificity, 90.3%). Incorporating NLR improved invasive UC detection (AUC=0.892; sensitivity, 75.0%; specificity, 100%). NLR was the most influential factor in UC detection. CONCLUSION: The UF-5000, when combined with the NLR, may enhance UC screening and contribute to a more effective diagnostic strategy."	bladder
Diagnostic Values of Electrochemiluminescent Detection of Urinary CYFRA21-1 and FDP and Their Combined Detection in Bladder Cancer.	BACKGROUND: Bladder cancer is the most common malignant tumor in the urinary system. The acquisition of urine samples has the advantages of being rapid and painless, and it can directly contact the lesions. It is an ideal source of non-invasive tumor markers. The problems with urine markers are low specificity, the propensity for false positives or missed detections, and there is no unified diagnostic standard to measure the test results, which limits the clinical application of urine markers. In this study, we evaluate the diagnostic values of Cytokeratin 19 fragment (CYFRA21-1), Fibrin/fibrinogen degradation products (FDP) and CYFRA21-1 + FDP in bladder cancer, with the objective to expand the application scope of urinary tumor markers in the diagnosis of bladder cancer. METHODS: We evaluated the performances of the CYFRA21-1 assay kit (electrochemiluminescence) and/or FDP assay kit (electrochemiluminescence) in detecting bladder cancer. CYFRA21-1 and FDP levels were determined in urine samples from 467 participants in South China Hospital of Shenzhen University and Shenzhen Luohu People's Hospital. We performed performance validation of the CYFRA21-1 and FDP kits, established normal biological reference intervals, and finally analyzed the data to assess their diagnostic efficacies alone or in combination. RESULTS: The bladder cancer group had significantly higher urinary levels of CYFRA21-1 and FDP than the control group. The areas under the receiver operating characteristic curves (ROC-AUCs) of CYFRA21-1, FDP, and CYFRA21-1 + FDP were 0.929, 0.857, and 0.935, respectively, for discriminating bladder cancer cases from controls. The ROC-AUC of CYFRA21-1 and FDP in combination was higher than that of any index alone. CONCLUSIONS: Both CYFRA21-1 and FDP have good diagnostic values in predicting bladder cancer. In addition, combined detection of urinary CYFRA21-1 and FDP by electrochemiluminescence has better differentiation ability compared with each index alone and may be used for early screening and recurrence monitoring in bladder cancer.	bladder
Treatment of Low-Grade Intermediate-Risk Non-Muscle Invasive Bladder Cancer With UGN-102: Outcomes From the 5-Year Long-Term Extension Study of the Single-Arm, Phase 2b Optima II Study.	INTRODUCTION: The OPTIMA II phase 2b study (NCT03558503) treated patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Efficacy and safety results have been reported for the 12-month parent study; here, we report 5-year follow-up data. PATIENTS AND METHODS: Patients who participated in the OPTIMA II study and achieved a complete response (CR) after 6 weekly doses of UGN-102 were followed for up to 9 months after initial CR. Those with CR at study completion were eligible to enroll in a further long-term follow-up (LTFU) study, during which there were no protocol-specified interventions/treatments, protocol-specified visits, or evaluations. Supervising physicians provided semiannual updates on patients' disease status. Duration of response (DoR) was calculated using the Kaplan-Meier method. RESULTS: Of the 41 patients achieving a CR at 3 months, 25 remained in CR at 12 months and 17 entered LTFU. For the 41 patients achieving a CR at 3 months the median Kaplan-Meier estimate of DoR was 24.2 months (95% confidence interval [CI], 9.72-42.09), with a median follow-up time of 35.8 months (95% CI, 10.78-60.98). For the 17 patients in the LTFU study the median DoR was 42.1 months (95% CI, 24.18-not estimable [NE]), with a median follow-up of 50.40 months (95% CI, 26.97-NE), CONCLUSION: These results demonstrate that treatment with UGN-102 results in clinically meaningful, and highly durable response in patients with LG-IR-NMIBC. UGN-102 may offer a promising non-surgical alternative to transurethral resection of bladder cancer (TURBT) for LG-IR-NMIBC patients.	bladder
Hypofractionated radiotherapy in the management of bladder cancer.	PURPOSE: Trimodal therapy, combining transurethral resection of the bladder tumour, radiotherapy, and concurrent radiosensitization, is an established bladder-preserving alternative to radical cystectomy in muscle-invasive bladder cancer. Hypofractionated radiotherapy has gained interest due to radiobiological advantages and logistical convenience, yet its efficacy and safety remain under evaluation. METHODS: A review of prospective phase II and III trials published between 2000 and 2025 was conducted in Medline using the search engine PubMed. Studies were included if they assessed hypofractionated radiotherapy (excluding stereotactic body radiotherapy) for non-metastatic muscle-invasive bladder cancer within a curative-intent using a trimodal therapy approach. Key endpoints included progression-free survival, overall survival, and toxicity. RESULTS: Seven prospective trials (five phase II, two phase III) were identified. The largest evidence come from the BC2001 and BCON trials, which demonstrated that a dose of 55Gy delivered in 20 fractions was non-inferior to a dose of 64Gy delivered in 32 fractions in terms of locoregional control and overall survival, with similar genitourinary and gastrointestinal toxicity rates. Additional studies confirmed comparable efficacy between hypofractionated and conventional fractionated radiotherapy regimens. Various concurrent systemic therapies were used, including cisplatin, 5-fluorouracil with mitomycin C, gemcitabine, and carbogen with nicotinamide, though no regimen showed clear superiority. Elective pelvic nodes irradiation remains controversial; one phase III trial showed no benefit, while recent data suggest a potential survival advantage without increased toxicity, even in hypofractionated protocols. CONCLUSION: Hypofractionated chemoradiotherapy is a safe and effective bladder-preserving strategy in selected patients with muscle-invasive bladder cancer. It offers comparable oncological outcomes and toxicity to conventional radiotherapy, with improved treatment efficiency. While systemic radiosensitization remains essential, further research is needed to optimize agents and clarify the role of pelvic nodes irradiation in hypofractionated settings.	bladder
Comparative Assessment of Chemotherapy Followed by Consolidative Radical Cystectomy Versus Chemoradiation for Clinically Node-Positive Urothelial Carcinoma of the Bladder.	CONTEXT: Patients with bladder cancer and clinically positive pelvic lymph nodes (cN+) have poor prognosis, and the optimal definitive treatment method remains controversial. OBJECTIVE: To compare survival outcomes between chemotherapy followed by radical cystectomy (RC) and chemoradiation (CRT) in patients with cN+ bladder cancer. METHODS: We queried the Surveillance, Epidemiology, and End Results (2000-2021) database to identify patients with cN+ bladder cancer treated with CRT or chemotherapy and RC. Cumulative incidence functions, Fine-Gray model, and Cox proportional hazards were used for the survival analysis. Inverse probability treatment weighting (IPTW) was used to adjust for confounders. The primary endpoints were cancer-specific mortality (CSM) and all-cause mortality (ACM). RESULTS: Among 552 patients identified, 175 (32%) received CRT and 377 (68%) underwent chemotherapy plus RC, and 5-year ACM was 75% (95% confidence interval [CI]: 71%-78%). RC and CRT were associated with 5-year CSM of 62% (95% CI: 57%-67%) and 72% (95% CI: 65%-78%), and 5-year ACM of 70% (95% CI: 65%-75%) and 85% (95% CI: 75%-90%), respectively. After IPTW, on multivariable Cox proportional hazard analysis adjusted for nodal and tumor staging, age, gender, tumor size and race, RC was associated with a significantly lower risk of CSM (hazard ratio [HR]: 0.47, 95% CI: 0.37-0.60, P < .001) and ACM (HR: 0.53, 95% CI: 0.46-0.60, P < .001). CONCLUSIONS: Patients with cN+ bladder cancer who received CRT had a worse prognosis compared to those who underwent chemotherapy followed by RC. The incorporation of more effective systemic therapies is required to improve outcomes, as in our analysis, only one in four cN+ patients survived beyond 5 years.	bladder
IHC-based molecular classification in muscle-invasive urothelial bladder carcinoma: Prognostic and predictive value toward a clinically applicable IHC marker panel - A systematic review.	Urothelial bladder carcinoma (UBC) is a heterogeneous disease, characterized by variable treatment responses and outcomes, attributed to its underlying molecular diversity. Molecular classification has advanced our understanding of UBC, but remains limited by cost and complexity. Immunohistochemistry (IHC) offers an accessible, cost-effective alternative for routine subtype classification. We aimed to evaluate the predictive role of IHC-based classification of UBC on oncological outcomes and response to treatment, as well as to identify key IHC markers for routine use. A systematic literature search of PubMed and Scopus was conducted in January 2025, following PRISMA guidelines. Using the PICOS framework, we included post-2020 observational studies on muscle-invasive UBC patients classified by IHC into molecular subtypes, correlating these subtypes with oncological outcomes and treatment responses. Luminal subtypes generally exhibit better PFS, DSS and OS, although some studies report mixed results. The basal subtype shows better RFS compared to double-negative subtype and demonstrates a significantly better response to neoadjuvant chemotherapy (NAC). Double-positive subtypes often have improved OS, while double-negative subtypes consistently show the worst outcomes. Commonly used IHC markers include GATA3 and CK5/6 for identifying luminal and basal subtypes, respectively. Additionally, p16 helps distinguish Luminal Unstable from Luminal Papillary or Genomically Unstable (GU) subtypes, EGFR refines basal subtype classification and vimentin differentiates rare mesenchymal-like subtypes. We showed that IHC-based classification is a practical, promising tool for UBC patient stratification, outcome and response to treatment prediction. By identifying key IHC markers, we proposed a standardized panel to improve consistency and reproductibility in clinical practice and research.	bladder
Droplet digital PCR assay for precise determination of FRS2 gene copy number in bladder cancer.	OBJECTIVE: To establish and validate a droplet digital PCR (ddPCR) assay for quantifying FRS2 gene copy number in formalin-fixed paraffin-embedded (FFPE) bladder cancer tissue samples, and to evaluate its analytical performance. METHODS: The ddPCR assay was developed using FRS2 as the target gene and RPP30 as the reference gene. Artificial plasmids, genomic DNA from urinary sediment of healthy individuals and cell lines were used as templates to assess the assay's precision, minimum reliable input DNA, and linearity. Fluorescence in situ hybridization (FISH) was employed to validate the accuracy of the ddPCR results. RESULTS: One-dimensional fluorescence amplitude plots showed clear separation between positive and negative droplets for both FRS2 and RPP30. Duplex detection of FRS2 and RPP30 within the same reaction showed no interference between primers or probes. The assay exhibited excellent repeatability and precision, with intra-assay coefficient of variation (CV)% of 2.58% and 3.75%, and inter-assay CV% of 2.68% and 3.79%, across 20 ng and 2 ng input levels, respectively. The minimum reliable input DNA amount was determined to be 2 ng, and a strong linear relationship was observed (R(2) >0.99). Compared to FISH, the ddPCR assay showed 100% sensitivity, 100% specificity, and a kappa value of 1. CONCLUSION: The developed ddPCR assay enables accurate and reliable quantification of FRS2 copy number in FFPE samples, offering a promising tool for auxiliary diagnosis and prognostic assessment in bladder cancer.	bladder
Optimizing cystectomy outcomes in muscle-invasive bladder cancer: what's new in 2025?	INTRODUCTION: Radical cystectomy (RC) remains the gold standard surgical treatment for muscle-invasive bladder cancer (MIBC). It is a technically complex procedure with considerable short- and long-term morbidity, even in experienced hands. AREAS COVERED: This review highlights recent advances in the multidisciplinary management of MIBC across the pre-, peri-, and post-operative phases. Improvements in surgical technique, peri-operative care pathways, and systemic therapies - including immunotherapy - have transformed outcomes. A targeted literature search was conducted using PubMed, Scopus, and Web of Science for English-language articles from 2015-2024, focusing on prospective studies from seminal clinical trials. Salient strategies were selected for inclusion based on clinical relevance and impact on patient outcomes. EXPERT OPINION: Optimizing outcomes for patients undergoing RC requires an evidence-based, patient-centered approach. The addition of immunotherapy in the peri-operative setting has changed the standard of care. In the future, peri-operative treatment decisions may be guided by biomarkers such as circulating tumor DNA. Additionally, optimizing patient comorbidities, delivering individualized patient education, and adhering to enhanced recovery protocols remain essential to optimizing patient outcomes.	bladder
Neolactotetraosylceramide enables urinary detection of bladder cancer.	Glycosphingolipids (GSLs) are promising cancer biomarkers. Using multiplexed capillary gel-electrophoresis with laser-induced fluorescence detection (xCGE-LIF), we profile GSLs in bladder cancer (BC) tissues and find a significant increase in neolactotetraosylceramide (nLc4) compared to matched normal tissue (n = 30). Immunofluorescence confirms tumor-specific nLc4 expression in both non-muscle-invasive BC (NMIBC) and muscle-invasive BC (MIBC), colocalizing with luminal and basal urothelial markers. Analysis of paired tissue/urine samples, along with BC cell lines, reveals secretion of nLc4 associated with extracellular vesicles in MIBC. Urine profiling shows elevated nLc4 levels in BC patients (n = 16) versus controls (n = 50; area under the curve [AUC] 0.75; accuracy 82%). To support clinical translation, we apply an anti-nLc4 ELISA in a discovery cohort (n = 18) and a multi-center validation cohort (n = 123). In the validation set, urinary nLc4 levels are significantly elevated in MIBC (AUC 0.78; accuracy 64%) and increase with disease severity. These findings support the potential of urinary nLc4 as a non-invasive biomarker for BC detection.	bladder